TMS vs. SSRIs: What Makes the Brain Respond Differently?

When it comes to treating depression, two approaches have emerged as frontrunners: traditional antidepressant medications like selective serotonin reuptake inhibitors (SSRIs) and non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS). While both are used to target depressive symptoms, they do so in fundamentally different ways. Understanding how the brain responds to each treatment can be the key to finding the right path toward healing—especially for individuals who haven’t responded well to medications.

In this article, we’ll unpack the differences between TMS and SSRIs, how they affect the brain, and why patients may respond better to one over the other.

How SSRIs Work in the Brain

SSRIs are one of the most commonly prescribed antidepressants. Medications like fluoxetine (Prozac), sertraline (Zoloft), and escitalopram (Lexapro) fall under this category. Their primary mechanism is to increase the availability of serotonin, a neurotransmitter that influences mood, in the brain.

They do this by blocking the reabsorption (or reuptake) of serotonin into neurons, making more of it available to improve the transmission of messages between brain cells. Over time—typically 4 to 6 weeks—this increased serotonin activity can help stabilize mood and reduce depressive symptoms.

However, SSRIs work on chemical signaling broadly across the brain. That means the effect isn’t targeted.

For some, this lack of specificity results in side effects like:

• Weight gain

• Sexual dysfunction

• Emotional numbness

• Insomnia or drowsiness

• Gastrointestinal issues

Additionally, not everyone responds to SSRIs. According to the STAR*D study, nearly one-third of patients with major depressive disorder (MDD) do not experience remission after multiple medication trials.

How TMS Works in the Brain

TMS, or transcranial magnetic stimulation, takes a completely different approach. Rather than altering neurotransmitter levels chemically, TMS uses magnetic pulses to directly stimulate regions of the brain that are underactive in people with depression—particularly the left dorsolateral prefrontal cortex (DLPFC).

This part of the brain plays a key role in mood regulation, executive functioning, and emotional processing. With repeated stimulation, TMS promotes neuroplasticity—the brain’s ability to adapt and reorganize itself. Essentially, TMS “reminds” certain brain circuits how to function properly, restoring balance without the need for daily medication.

TMS is:

• FDA-approved for treatment-resistant depression

• Non-invasive and non-sedating

• Administered in-office, with patients remaining awake

• Typically involves daily sessions over a 4-6 week period

• Often well-tolerated with few side effects (most commonly, mild scalp discomfort or headache)

Most importantly, TMS is targeted. It stimulates specific brain regions rather than altering neurotransmitter levels system-wide, which is why many patients experience fewer side effects.

TMS vs. SSRIs: Why the Brain Responds Differently

The brain’s response to SSRIs vs. TMS comes down to mechanism of action and neural specificity.

• SSRIs rely on chemical modulation. They aim to balance neurotransmitters like serotonin and dopamine, but this happens across many brain systems—some related to mood and others not. It’s a bit like trying to brighten one room in your house by turning on every light.

• TMS provides focused stimulation. It activates the exact region responsible for mood regulation. Think of it as switching on a light in the one room that needs it most.

Some individuals may have biological or genetic factors that affect how well they metabolize medications, making SSRIs less effective or harder to tolerate. Others may have specific circuit dysfunctions that respond better to electrical or magnetic stimulation, making TMS a more natural fit.

Recent imaging studies even suggest that TMS normalizes brain activity patterns in ways that medications can’t. In fact, some patients who previously failed multiple medications go on to experience full remission with TMS.

When to Consider TMS Over SSRIs

If you or a loved one has tried multiple antidepressants with little relief—or experienced intolerable side effects—TMS may be worth considering.

You might benefit from TMS if:

You’ve been diagnosed with major depressive disorder You’ve tried at least one or two SSRIs without success You’re looking for a non-systemic, non-drug option You prefer an approach with minimal daily maintenance You want to avoid medication side effects

TMS is also increasingly used in combination with therapy or wellness strategies to create a more holistic, personalized treatment plan.

The Bottom Line

In the conversation of TMS vs SSRIs, the right answer is deeply personal. Some individuals respond well to medication, others find relief through TMS, and many benefit from a combination of approaches. What matters most is understanding the unique way your brain responds to treatment—and working with a provider who understands both the science and the soul of healing.

At Goodwin Health Café, we’re proud to offer cutting-edge TMS therapy in a warm, welcoming environment that puts you first. Our team takes the time to evaluate your full history, explore all treatment options, and help you feel empowered in your care.

Ready to take the next step?Visit us at www.goodwinhealthcafe.com5625 N. Wall St. Suite 100, Spokane, WA 99205

Let’s find what works for your brain—together.